2. Academic Validation
  3. Incorporation of nitric oxide donor into 1,3-dioxyxanthones leads to synergistic anticancer activity

Incorporation of nitric oxide donor into 1,3-dioxyxanthones leads to synergistic anticancer activity

  • Eur J Med Chem. 2018 May 10:151:158-172. doi: 10.1016/j.ejmech.2018.03.072.
Jie Liu 1,  Cao Zhang 2,  Huailing Wang 3,  Lei Zhang 2,  Zhenlei Jiang 2,  Jianrun Zhang 2,  Zhijun Liu 2,  Heru Chen 4
Affiliations

Affiliations

  • 1 Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Department of Allergy, The Third Affiliated Hospital of Shenzhen University, Shenzhen 518020, PR China.
  • 2 Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
  • 3 School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.
  • 4 Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, PR China. Electronic address: thrchen@jnu.edu.cn.
PMID: 29609121 DOI: 10.1016/j.ejmech.2018.03.072
Abstract

Fifty 1,3-dioxyxanthone nitrates (4a ∼ i-n, n = 1-6) were designed and synthesized based on molecular similarity strategy. Incorporation of nitrate into 1,3-dioxyxanthones with electron-donating groups at 6-8 position brought about synergistic Anticancer effect. Among them, compound 4g-4 was confirmed the most active agent against HepG-2 cells growth with an IC50 of 0.33 ± 0.06 μM. It dose-dependently increased intramolecular NO levels. This activity was attenuated by either NO scavenger PTIO or mitochondrial aldehyde dehydrogenase (mtADH) inhibitor PCDA. Apoptosis analysis indicated different contributions of early/late Apoptosis and necrosis to cell death for different dose of 4g-4. 4g-4 arrested more cells on S phase. Results from Western Blot implied that 4g-4 regulated p53/MDM2 to promote Cancer cell Apoptosis. All the evidences support that 4g-4 is a promising anti-cancer agent.

Keywords

Ati-Cancer; Nitrates; Synergistic effect; Xanthones; p53/MDM2.

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